Hepatitis C

By Stephen Holt, MD, PhD, FACP

• What is Hepatitis C?
• How is it Transmitted?
• Who Is At Risk?
• Symptoms
• Other Signs and Symptoms that May Exist?
• Types
• How is it Diagnosed?
• Conventional Medical Treatment
• Best Treatment
• Alternative Therapies
• Suggested Articles

What is Hepatitis C?

Hepatitis C virus (HCV) is a spherical, enveloped, single-stranded RNA virus belonging to the family flaviviridae. Discovered in 1989, HCV explained 90 percent of non-A non-B (NANB) cases of hepatitis.

• It is the most common cause of chronic liver disease in the United States and the prevalence of Hepatitis C virus infection is increasing worldwide.
• The World Health Organization estimates that 71 million individuals throughout the world are infected with chronic HCV. Globally, 1.75 million people are newly infected each year.
• The Centers for Disease Control (CDC) estimate that 3.5 million people in America have chronic Hepatitis C.
• 75-85% of all acute Hepatitis C infections will develop to chronic Hepatitis C and 10-20% of those patients will develop cirrhosis over a period of 20-30 years.
• Chronic Hepatitis C is the most common reason that a person will need to undergo a liver transplant in the U.S.
• Prior infection with Hepatitis C does not protect you against another infection with the same or different genotype later.

How is it Transmitted?

Hepatitis C is primarily transmitted through blood-to-blood contact. Known as the percutaneous route, blood from an infected person must penetrate the barrier of the skin and enter the bloodstream of another person. The virus may also be found in internal body fluids surrounding the heart, lungs, bone joints (like the shoulder and elbows) and spinal fluid. In persons who are infected, HCV may produce approximately one trillion new viral particles each day in a steady state of viral replication. As documented by occupational exposure statistics, Hepatitis C is approximately seven times more infectious than HIV.

The most common routes of transmission include:

• Blood and blood product transfusions
• Intravenous drug use
• Intranasal drug use
• Healthcare and occupational exposure
• Medical procedures
• Tattooing and body piercing
• Sexual contact
• Household contact
• Childbirth

Who Is At Risk?

Recent studies suggest that HCV may survive on environmental surfaces at room temperature at least 16 hours, but no longer than 4 days.

The following individuals are at risk:

• Anyone who injected illegal drugs, including those who injected once or a few times many years ago
• People who were treated for clotting problems with a blood product made before 1987 when more advanced methods for manufacturing the products were developed
• People who were notified that they received blood from a donor who later tested positive for Hepatitis C
• People who received a blood transfusion or solid organ transplant before July 1992 when better testing of blood donors became available
• Long-term hemodialysis patients
• People who have signs or symptoms of liver disease (e.g., abnormal liver enzyme tests)
• Healthcare workers after exposures (e.g., needle sticks or splashes to the eye) to HCV-positive blood on the job
• Children born to HCV-positive women
• People who have had multiple sexual partners, particularly where there is a history of a sexually transmitted disease
• Household members of an infected person
• People who have acquired a tattoo or who have had a body part pierced

Symptoms

Hepatitis C can be either acute or chronic. Only a small percentage, about 25 to 35 percent, of individuals with acute HCV will manifest any symptoms at all. These symptoms are similar to other cases of acute hepatitis, including flu-like symptoms, joint aches or mild skin rash. People with Hepatitis B, who also become infected with acute Hepatitis C, are particularly likely to experience a severe course of Hepatitis C.

Most people diagnosed with chronic Hepatitis C are surprised to find out they have this virus because symptoms, even in the advanced stages, are usually absent. Even those who have advanced to cirrhosis may only complain of vague abdominal discomfort, often in the area over the liver. Others may have a decreased appetite, weight loss and depression.

Once a person is infected with the virus, it is difficult for the body to clear it. Unlike those individuals with either Hepatitis A or B, approximately 85 percent of those with acute Hepatitis C develop chronic Hepatitis C. This is because HCV can mutate into a stronger quasi-species variant that escapes the immune system’s attempt to eradicate the virus. This explains why long-term response rates had been so disappointing and why it is so difficult to create a vaccination against HCV.

Other Signs and Symptoms that May Exist?

People with the virus may exhibit symptoms and signs of infection that manifest in organs other than the liver. Known as extrahepatic manifestations, or immune-complex mediated diseases, these symptoms arise from the immune system’s effort to fight off the HCV infection. Examples of extrahepatic manifestations include:

• Skin diseases such as vasculitis, porphyria cutanea tarda (PCT) and lichen planus
• Blood-related diseases such as cryoglobulinemia
• Endocrine disorders such as thyroid disease

Types

A genotype is a classification of a virus based on the genetic material in the RNA strands of the virus. There are six distinct genotypes of the virus in the world with multiple sub-types in each genotype class. Another reason chronic Hepatitis C is so difficult to treat is because of these multiple distinct genotypes. A patient is usually only infected with one genotype, but each genotype is actually a mixture of closely-related viruses called quasi-species. These quasi-species have the ability to mutate very quickly and become immune to current treatments.

Following is a list of the different genotypes of chronic HCV:

Genotype 1a
Genotype 1b
Genotype 2a, 2b, 2c & 2d
Genotype 3a, 3b, 3c, 3d, 3e & 3f
Genotype 4a, 4b, 4c, 4d, 4e, 4f, 4g, 4h, 4i & 4j
Genotype 5a
Genotype 6a

For physicians, knowing the genotype of the virus is helpful in making a therapeutic recommendation. Once the genotype is identified, it need not be tested again; genotypes do not change during the course of infection.

How is it Diagnosed?

Most people find out they have the virus by a routine physical examination. Since the symptoms may mimic a cold or flu, many people do not go to the doctor for treatment, thus, they are left undiagnosed. Some people discover they have it when they do visit a doctor for symptoms such as fatigue, jaundice, loss of appetite or an extrahepatic manifestation.

The Hepatitis C test used for blood donor screening is an ELISA (enzyme-linked immunosorbent assay). Approximately 40 percent of those people who test positive for HCV by this screening blood test actually do not have Hepatitis C. This is known as a false positive test. Therefore, people testing positive should be tested again with a more accurate method known as a RIBA (recombinant immunoblot assay).

A false negative occurs in testing when people with early infections have not developed antibody levels high enough that the test can measure. In addition, some people may lack the immune response necessary for the test to work well. In these people, research-based tests such as the PCR (polymerase chain reaction) may be considered.

Following exposure to HCV, seven out of ten people test positive immediately when symptoms begin and about nine out of ten people test positive within three months after symptoms begin. It is important to note that many people who have Hepatitis C have no symptoms.

Conventional Medical Treatment

Not all people who have been diagnosed with Hepatitis C need treatment, especially in the case of acute Hepatitis. Medication may be prescribed, however, bed rest, drinking plenty of fluids, avoidance of alcohol and eating a healthy diet will be recommended by the doctor. It is important to work closely with one’s doctor and follow up with tests to make sure the virus has cleared the body.

Some people won’t be treated because they don’t know they have the Hepatitis C virus.

Individuals who have been diagnosed with chronic Hepatitis C will probably be treated with various combinations of medication. The type of treatment as well as the length of treatment for Hepatitis C depends on the genotype of the virus. Working closely with one’s physician, using an open line of communication will help in determining the best course of action.

Interferon

Some treatment options for Hepatitis C include medications with and without interferon. Once in the bloodstream, interferon interferes with the Hepatitis C virus’ ability to replicate. In addition, interferon appears to build up the immune system’s disease fighting T helper-1 cells so that they are strong enough to kill off the Hepatitis C viruses.

Side effects from interferon can be unpleasant and sometimes serious, leading to dose reduction or discontinuation of treatment. All side effects should be reported to one’s doctor right away for management of symptoms and to prevent serious complications from occurring.

Not all people experience the same side effects, nor are all side effects necessarily severe. Some people experience few or no side effects at all. Having a good support system in place prior to starting treatment will help in managing side effects whether few or many. Family, friends, and support groups can be helpful to most people during difficult times while undergoing treatment.

Side effects from interferon may include:

• Persistent flu-like symptoms (including body aches and headaches)
• Nausea
• Fatigue
• Loss of appetite
• Diarrhea
• Insomnia
• Mental and psychiatric symptoms, including depression, irritability, anxiety, mania and trouble concentrating
• Bone marrow suppression
• Anemia
• Dehydration
• Mouth sores
• Changes in the way food and beverages taste
• Skin rashes and itching
• Dry, brittle nails
• Injection site reactions (pain, irritation, swelling or infection)
• Hair loss
• Vision or eye problems (rare but can be serious)
• Libido changes (decreased interest in sex)
• Menstrual and menopausal changes

Ribavirin

Ribavirin, an antiviral drug that suppresses the Hepatitis C virus is commonly used in conjunction with other medications to treat Hepatitis C. When used alone, Ribavirin promptly brings down liver enzymes but the results don’t last long and liver enzymes go back up. Similar to interferon side effects, Ribavirin has been known to cause anemia, thyroid disease, hypertension and depression. Pregnant women and anyone with cardiovascular disease should not take Ribavirin. Ribavirin can cause birth defects so it is important for both men and women to use an effective form of contraception.

Treatments and Genotype

Historically, HCV genotype 1 was the most difficult to treat, however new treatment options have come available. Toward the end of 2013 the FDA approved two new medications. Olysio capsules are used in combination with pegintereferon alfa and ribaviron or in combination with sofosbuvir for hepatitis c genotype 1 patients. The once-daily oral prescription medication, Sovaldi (sofosbuvir), was also approved for use in combination with peginterferon alfa and ribavirin OR ribavirin. Its efficacy was established in patients with hepatitis c genotypes 1, 2, 3 or 4.

On October 4, 2014 a new medication called Harvoni (ledipasvir and sofosbuvir) was approved combining sofosbuvir and ledipasvir. This single daily tablet for the treatment of HCV genotype 1 is not used in combination with interferon. Two months later, Viekira Pak (ombitasvir, paritaprevir and ritonavir) was approved for those with HCV genotype 1 including those patients with compensated cirrhosis.

Hepatitis C genotype 3 is the second most prevalent in the United States. In July 2015 Daklinza was approved by the FDA for use with sofosbuvir as the first 12-week, all-oral treatment option for patients with HCV genotype 3.

Also in 2015 Technivie was approved for use in combination with ribavirin for the treatment of genotype 4 and was the first drug approved to treat genotype 4 without having to use interferon.

In 2016, Zepatier was approved by the FDA for use with or without ribavirin for genotypes 1 and 4. Later that same year Epclusa was approved as the first single tablet regimen for patients with HCV genotype 2 and 3 without ribavirin.

Most recently, Vosevi was introduced in 2017 as the first single tablet, once daily medication approved for patients with genotypes 1-6 followed soon thereafter by Mavyret’s approval as the first 8 week treatment for all Hepatitis C genotypes.

There are contraindications with each of these medications and it is important to note that not all people are candidates for receiving them. Speak with your specialist.

For more information about HCV treatment options for various genotypes visit http://www.hepatitiscentral.com/medications-to-treat-hepatitis-c-a-timeline/.

Other Options

Finally, if the liver is severely damaged, a liver transplant may be recommended. End-stage liver disease (cirrhosis) due to chronic infection is the number one reason for liver transplantation in the United States. During the transplant procedure, the diseased liver will be replaced with a healthy liver from an organ donor or from a live donor who donates a portion of their healthy liver. However, contrary to popular misconception, a liver transplant is not a cure for Hepatitis C. Unfortunately, the virus recurs in the new liver in almost all cases, with fibrosis (scarring of the liver) or cirrhosis occurring in 10% to 30% of patients in as little as 5 years after the transplant.

Further studies are needed to develop better strategies to prevent recurrence of infection after a liver transplant as well as better treatment protocols after reinfection of the liver has occurred.

Best Treatment

You need to communicate with your health care provider to determine the best course of action. Each medication and combination of medications has their own prescribing recommendations. Due to the various contraindications for each medication, which option is BEST for you needs to be determined between you and your specialist.

Alternative Therapies

The three most common reasons given for choosing to use Complementary and Alternative Medicine (CAM) therapies are to improve quality of life, boost the immune system and slow disease progression.

What approaches are commonly seen for Hepatitis C?

There are many holistic and natural approaches for dealing with Hepatitis C. The most respectable approaches focus on protecting and supporting the liver and keeping the immune system healthy. Keep in mind that any alternative therapies claiming to cure or treat hepatitis c should be avoided.

The most popular alternative therapies to support the liver for those with Hepatitis C are:

1. Single Herbal Remedies – This is the most popular CAM route chosen for treating HCV. Milk thistle in particular is the most researched and supported supplement to aid in liver health. Milk thistle’s active ingredient, silymarin, is an antioxidant, hepatoprotectant, anti-inflammatory and stimulates the growth of new liver cells. Other herbal remedies include lecithin, licorice root, schizandra and Eclipta alba. Similarly, certain herbs and supplements are known to cause harm to the liver such as kava kava and vitamin A.
2. Chinese and Japanese Herbal Therapy
3. Acupuncture
4. Massage
5. Antioxidants

This information is intended for educational purposes only and should not be used in any other manner. This information is not intended to substitute for informed medical advice. You should not use this information to diagnose or treat a health problem or disease without consulting with a qualified health care provider.

Suggested Articles

• Living with Hepatitis C: Is an Occasional Drink Okay?
• Sexual Transmission of Hepatitis C
• Factors that Raise the Risk of Hepatitis C Relapse
• Pain Relievers and Hepatitis C

About the Author

Stephen Holt, MD, PhD, FACP

Stephen Holt, M.D. is a Distinguished Professor of Medicine NYCPM (Emerite) and a medical practitioner in New York State. He has published many peer-review papers in medicine and he is a best-selling author with more than twenty books in national and international distribution. He has received many awards for teaching and research. Dr. Holt is a frequent lecturer at scientific meetings and healthcare facilities throughout the world. He is a best selling author and the founder of the Holt Institute of Medicine.